We have a continuing program which is aimed at establishing the foundation for the use of fluorocarbons and fluorocarbon emulsions in biology and medicine. These inert, non-metabolizable, synthetic organic oxygen solvents offer great promise as blood substitutes and for controlling tissue oxygen tensions in ischemic organic diseases. We are defining the requirements for vapor pressure, tissue permeability, emulsion stability in vitro and in vivo, critical solution temperature, purity and chemical structure. We are carefully scrutinizing the effects of perfluorinated organic compounds on the ultrastructure of a number of organs, particularly liver and spleen. We are specially interested in the cyclic all-carbon perfluorinates because of their property of being readily transpired from the liver, through the lungs and skin, following their intravascular use and because they can be manufactured in pure form. Using toxicity tests and transpiration measurements in mice, and blood addition and replacement studies in rats, cats, and non-human primates, we have selected a few compounds as being most desirable. Among these are perfluorinated decalins, adamantanes, bicyclononanes, bicyclodecanes, and straight and branched paraffinics.